Up-regulation and activation of proteinase-activated receptor 2 in early and delayed radiation injury in the rat intestine: influence of biological activators of proteinase-activated receptor 2

Proteinase-activated receptor 2 (Par2, F2rl1, also designated PAR-2 or PAR2) is prominently expressed in the intestine and has been suggested as a mediator of inflammatory, mitogenic and fibrogenic responses to injury. Mast cell proteinases and pancreatic trypsin, both of which have been shown to affect the intestinal radiation response, are the major biological activators of Par2. Conventional Sprague-Dawley rats, mast cell-deficient rats, and rats in which pancreatic exocrine secretion was blocked pharmacologically by octreotide underwent localized irradiation of a 4-cm loop of small bowel. Radiation injury was assessed 2 weeks after irradiation (early, inflammatory phase) and 26 weeks after irradiation (chronic, fibrotic phase). Par2 expression and activation were assessed by in situ hybridization and immunohistochemistry, using antibodies that distinguished between total (preactivated and activated) Par2 and preactivated Par2. Compared to unirradiated intestine, irradiated intestine exhibited increased Par2 expression, particularly in areas of myofibroblast proliferation and collagen accumulation, after both single-dose and fractionated irradiation. The majority of Par2 expressed in fibrotic areas was activated. Postirradiation Par2 overexpression was greatly attenuated in both mast cell-deficient and octreotide-treated rats. The severity of acute mucosal injury did not affect postirradiation Par2 expression. Mast cells and pancreatic proteinases may exert their fibro-proliferative effects partly through activation of Par2. Par2 may be a potential target for modulating the intestinal radiation response, particularly delayed intestinal wall fibrosis.     

口腔鳞状细胞癌中VEGF、Bcl-2的表达及意义

目的研究血管内皮细胞生长因子VEGF、Bcl-2在口腔鳞状细胞癌(OSCC)中的表达及意义。方法应用免疫组化SP法检测。结果在OSCC不同分化及TNM分期病例中VEGF阳性表达率无显著差异,但Ⅳ期VEGF阳性表达级别比Ⅰ期病例有显著增高。颈淋巴结转移组的VEGF比无颈淋巴结转移组阳性率高(P<0.05)。OSCC高分化组中Bcl-2的表达率比中低分化组明显低(P<0.05)。VEGF阳性级别越高的病例组,Bc-l2的表达率越高。结论在口腔鳞癌中VEGF、Bcl-2的表达有显著的正相关关系。     

Effects of permafrost degradation on ecosystems

Permafrost, covering approximately 25% of the land area in the Northern Hemisphere, is one of the key components of terrestrial ecosystem in cold regions. As a product of cold climate, permafrost is extremely sensitive to climate change. Climate warming over past decades has caused degradation in permafrost widely and quickly. Permafrost degradation has the potential to significantly change soil moisture content, alter soil nutrients availability and influence on species composition. In lowland ecosystems the loss of ice-rich permafrost has caused the conversion of terrestrial ecosystem to aquatic ecosystem or wetland. In upland ecosystems permafrost thaw has resulted in replacement of hygrophilous community by xeromorphic community or shrub. Permafrost degradation resulting from climate warming may dramatically change the productivity and carbon dynamics of alpine ecosystems. This paper reviewed the effects of permafrost degradation on ecosystem structure and function. At the same time, we put forward critical questions about the effects of permafrost degradation on ecosystems on Qinghai–Tibetan Plateau, included: (1) carry out research about the effects of permafrost degradation on grassland ecosystem and the response of alpine ecosystem to global change; (2) construct long-term and located field observations and research system, based on which predict ecosystem dynamic in permafrost degradation; (3) pay extensive attention to the dynamic of greenhouse gas in permafrost region on Qinghai–Tibetan Plateau and the feedback of greenhouse gas to climate change; (4) quantitative study on the change of water-heat transport in permafrost degradation and the effects of soil moisture and heat change on vegetation growth.     

Pharmacophore-based discovery of triaryl-substituted imidazole as new telomeric G-quadruplex ligand

Discovery of potent and selective ligands for telomeric G-quadruplex DNA is a challenging work. Through a combination approach of pharmacophore model construction, model validation, database virtual screening, chemical synthesis and interaction evaluation, we discovered and confirmed triaryl-substituted imidazole TSIZ01 to be a new telomeric G-quadruplex ligand with potent binding and stabilizing activity to G-quadruplex DNA, as well as a 8.7-fold selectivity towards telomeric G-quadruplex DNA over duplex DNA.     

The X-linked tumor suppressor TSPX interacts and promotes degradation of the hepatitis B viral protein HBx via the proteasome pathway

Hepatitis B virus (HBV) infection is a major risk for hepatocellular carcinoma (HCC), and it is a serious global health problem with two billion people exposed to it worldwide. HBx, an essential factor for viral replication and a putative oncoprotein encoded by the HBV genome, has been shown to promote oncogenic properties at multiple sites in HBV-infected liver cells. The expression level of HBx closely associates with the development and progression of HCC, therefore the mechanism(s) regulating the stability of HBx is important in oncogenesis of HBV-infected cells. We demonstrate that the X-linked tumor suppressor TSPX enhances the degradation of HBx through the ubiquitin-proteasome pathway. TSPX interacts with both HBx and a proteasome 19S lid subunit RPN3 via its C-terminal acidic tail. Most importantly, over-expression of RPN3 protects HBx from, and hence acts as a negative regulator for, proteasome-dependent degradation. TSPX abrogates the RPN3-depedent stabilization of HBx, suggesting that TSPX and RPN3 act competitively in regulation of HBx stability. Since mutation and/or epigenetic repression of X-located tumor suppressor gene(s) could significantly predispose males to human cancers, our data suggest that TSPX-induced HBx degradation could play key role(s) in hepatocarcinogenesis among HBV-infected HCC patients.     

Optimum induction of recombinant thymidine phosphorylase and its application

Recombinant E. coli pDEOA was constructed and lactose can be used instead of IPTG to induce the expression of thymidine phosphorylase by pDEOA. The use of lactose at concentrations higher than 0.5 mmol/L had an induction effect similar to that of IPTG but resulted in a longer initial induction time and better cell growth. The thymidine phosphorylase induced by lactose was very stable at 50°C. Intact pDEOA cells induced by lactose can be used as a source of thymidine phosphorylase. Under standard reaction conditions, several deoxynucleosides were effectively produced from thymidine.     

Serum early prostate cancer antigen (EPCA) level and its association with disease progression in prostate cancer in a Chinese population

Background

Early prostate cancer antigen (EPCA) has been shown a prostate cancer (PCa)-associated nuclear matrix protein, however, its serum status and prognostic power in PCa are unknown. The goals of this study are to measure serum EPCA levels in a cohort of patients with PCa prior to the treatment, and to evaluate the clinical value of serum EPCA.

Methods

Pretreatment serum EPCA levels were determined with an ELISA in 77 patients with clinically localized PCa who underwent radical prostatectomy and 51 patients with locally advanced or metastatic disease who received primary androgen deprivation therapy, and were correlated with clinicopathological variables and disease progression. Serum EPCA levels were also examined in 40 healthy controls.

Results

Pretreatment mean serum EPCA levels were significantly higher in PCa patients than in controls (16.84±7.60 ng/ml vs. 4.12±2.05 ng/ml, P<0.001). Patients with locally advanced and metastatic PCa had significantly higher serum EPCA level than those with clinically localized PCa (22.93±5.28 ng/ml and 29.41±8.47 ng/ml vs. 15.17±6.03 ng/ml, P = 0.014 and P<0.001, respectively). Significantly elevated EPCA level was also found in metastatic PCa compared with locally advanced disease (P<0.001). Increased serum EPCA levels were significantly and positively correlated with Gleason score and clinical stage, but not with PSA levels and age. On multivariate analysis, pretreatment serum EPCA level held the most significantly predictive value for the biochemical recurrence and androgen-independent progression among pretreatment variables (HR = 4.860, P<0.001 and HR = 5.418, P<0.001, respectively).

Conclusions

Serum EPCA level is markedly elevated in PCa. Pretreatment serum EPCA level correlates significantly with the poor prognosis, showing prediction potential for PCa progression.     

Reciprocal roles of DBC1 and SIRT1 in regulating estrogen receptor α activity and co-activator synergy

Estrogen receptor α (ERα) plays critical roles in development and progression of breast cancer. Because ERα activity is strictly dependent upon the interaction with coregulators, coregulators are also believed to contribute to breast tumorigenesis. Cell Cycle and Apoptosis Regulator 1 (CCAR1) is an important co-activator for estrogen-induced gene expression and estrogen-dependent growth of breast cancer cells. Here, we identified Deleted in Breast Cancer 1 (DBC1) as a CCAR1 binding protein. DBC1 was recently shown to function as a negative regulator of the NAD-dependent protein deacetylase SIRT1. DBC1 associates directly with ERα and cooperates synergistically with CCAR1 to enhance ERα function. DBC1 is required for estrogen-induced expression of a subset of ERα target genes as well as breast cancer cell proliferation and for estrogen-induced recruitment of ERα to the target promoters in a gene-specific manner. The mechanism of DBC1 action involves inhibition of SIRT1 interaction with ERα and of SIRT1-mediated deacetylation of ERα. SIRT1 also represses the co-activator synergy between DBC1 and CCAR1 by binding to DBC1 and disrupting its interaction with CCAR1. Our results indicate that DBC1 and SIRT1 play reciprocal roles as major regulators of ERα activity, by regulating DNA binding by ERα and by regulating co-activator synergy.     

Posters Part 1

Schima superba and Pinus massoniana distributed over large areas in southern China both are dominant species at Dinghushan Biosphere Reserve. In the present study, the changes of chlorophyll fluorescence and xanthophyll cycle in the leaves of S. superba and P. massoniana exposed to simulated acid rain (SAR) were measured. When exposed to high light, the PSII photochemistry efficiency (F _v/F _m), efficiency of energy conversion in PSII (ΦPSII) and photochemical quenching (qP) of both S. superba and P. massoniana all decreased when acidity of SAR increased. Regarding non-photochemical quenching (qN), S. superba exposed to SAR had higher value than control plants, but there was no significant difference between the respective seedlings of P. massoniana. As for xanthophyll cycle of the two plant species, the leaves of S. superba exposed to SAR showed a higher content of carotenoids and a higher ability to convert violaxanthin to zeaxanthin than leaves of P. massoniana, which was consistent with S. superba exhibiting a stronger resistance to high light than P. massoniana. Although both species were susceptible to acid rain as shown by our results, P. massoniana was more susceptible compared to S. superba. These results provide an insight into how to protect the forest ecosystem at Dinghushan Biosphere Reserve.